Because palmitoylethanolamide (PEA) has documented anti-inflammatory and neuroprotective properties, and because inflammation has been proposed as a contributing factor in some autism spectrum disorder (ASD) presentations, researchers have studied PEA as an add-on treatment alongside standard medications in children with autism. This article covers the one randomized controlled trial that has directly tested this, what it found, and what it explicitly did not test.
This is a topic that deserves precision rather than hype. PEA is a dietary supplement, not an FDA-approved treatment for autism spectrum disorder, and the research below tested PEA as an addition to an existing prescription medication in children with a specific symptom profile, not as a standalone intervention or a treatment for the core features of autism itself. Any decision about supplementing a child’s care should be made with the child’s treating physician or developmental pediatrician, not from a website article.
Key Takeaways
- A 2018 randomized, double-blind, placebo-controlled trial tested PEA as an add-on to risperidone (an antipsychotic commonly prescribed for irritability in autism) in 70 children ages 4 to 12 with autism and moderate to severe irritability [1].
- Over 10 weeks, the PEA plus risperidone group showed significantly greater improvement in irritability and hyperactivity/noncompliance scores than the placebo plus risperidone group.
- PEA did not significantly improve stereotypic (repetitive) behavior scores in this trial, meaning the benefit was specific to certain symptom domains, not the full range of autism-associated behaviors.
- This trial tested PEA as an adjunct to an existing prescription medication, not as a standalone or first-line treatment, and was conducted only in children, not adults.
- This remains a single trial from one research group; it has not yet been independently replicated at scale.
What the 2018 Trial Actually Tested
The trial, published in the Journal of Psychiatric Research, recruited 70 children ages 4 to 12 with an autism diagnosis and moderate to severe irritability, a symptom domain that includes tantrums, aggression, and self-injurious behavior and is a common reason families seek pharmacological treatment [1]. All participants were already being treated with risperidone, the standard prescription option for irritability in autism, and were randomly assigned to add either PEA or a placebo to their existing regimen for 10 weeks. Researchers used the Aberrant Behavior Checklist-Community Edition (ABC-C), a standard clinical rating scale, to measure outcomes across several behavioral domains.
What the Results Showed
At the 10-week endpoint, children in the PEA plus risperidone group showed significantly greater improvement than the placebo plus risperidone group on the irritability and hyperactivity/noncompliance subscales of the ABC-C. The researchers reported this as a large effect size for a psychiatric add-on trial. Notably, the trial did not find a significant difference between groups on the stereotypic behavior subscale, meaning PEA’s apparent benefit in this study was concentrated in irritability and hyperactivity rather than repetitive behaviors, one of the core diagnostic features of autism.
Research note: A scoping review of five human studies found endocannabinoid system alterations in autism, including decreased PEA, but also discrepant findings across studies [5].
The proposed rationale behind the trial connects to two mechanisms researchers have investigated in autism: neuroinflammation and glutamate excitotoxicity (excessive excitatory signaling that can be damaging to neurons over time). PEA has documented effects on both pathways in other research contexts, which is why the trial’s authors selected it as an add-on candidate rather than testing it as a standalone medication.
What This Trial Does Not Establish
It’s important to be direct about the limits of a single trial. This was PEA added to an existing antipsychotic medication, not PEA studied on its own, so the results cannot be used to conclude that PEA alone would produce the same benefit without risperidone. It only enrolled children with moderate to severe irritability, so it says nothing about children with autism who don’t have significant irritability symptoms, and nothing about adults. It did not test whether PEA affects the core diagnostic features of autism such as social communication differences, since the primary measured domains were irritability, hyperactivity, and stereotypy, not social or communication scores. Finally, as of this writing, this specific PEA-plus-risperidone trial design has not been independently replicated by another research group, which matters for how much weight a single trial’s findings should carry.
A review of randomized trials of autism irritability drugs lists PEA among agents, all adjunct to risperidone, that outperformed placebo, and notes that sample size, follow-up and effect size limit these trials [4].
Separately, one paper combined a mouse study (valproic acid-induced autism-like behavior) with a single case report of a 10-year-old boy, using a related but distinct combination, co-ultramicronized PEA with the flavonoid luteolin. The publisher has since issued an Expression of Concern on that paper because duplicated western blot control bands meant the results in Figure 2 could not be confirmed [2][3]. That is a different formulation and a much thinner evidence base than the randomized trial discussed above, and the two should not be conflated.
What Parents and Caregivers Should Know
If you’re considering PEA for a child with autism, the most defensible starting point based on the evidence is a conversation with the child’s prescribing physician, particularly if the child is already taking risperidone or a similar medication, since that is the specific context the positive trial evidence comes from. PEA should not be treated as a substitute for established interventions such as behavioral therapy, speech and occupational therapy, or prescribed medications where clinically indicated. Supplement quality and dosing in children is a separate consideration from the dosing used in adult chronic pain research covered elsewhere on this site, and any pediatric use should be guided by a physician rather than adult dosing guidelines.
Frequently Asked Questions
Does PEA treat the core symptoms of autism?
The available randomized trial did not find a significant effect on stereotypic (repetitive) behaviors, one of autism’s core diagnostic features. The measured benefit was in irritability and hyperactivity/noncompliance, which are common but not core diagnostic symptoms.
Was PEA tested alone or with another medication in the autism trial?
The 2018 randomized controlled trial tested PEA as an add-on to risperidone, an antipsychotic medication the children were already taking. The trial does not tell us how PEA would perform as a standalone treatment without risperidone.
Has the autism PEA trial been repeated by other researchers?
Not yet, as of this writing. This remains a single trial from one research group, and independent replication is an important next step before treating the finding as well established.
Should I give my child PEA without talking to their doctor?
No. Any decision to add a supplement to a child’s care, especially a child who may already be on prescription medication, should be made together with their treating physician or developmental pediatrician, not based on a single research article.
References
- Khalaj M, Saghazadeh A, Shirazi E, et al. Palmitoylethanolamide as adjunctive therapy for autism: Efficacy and safety results from a randomized controlled trial. J Psychiatr Res (2018). PMID 29807317
- Bartolomeo Bertolino et al. Beneficial Effects of Co‐Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism. CNS Neuroscience & Therapeutics (2016). PMID 27701827
- CNS neuroscience & therapeutics EXPRESSION OF CONCERN: Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism. CNS neuroscience & therapeutics (2024). PMID 39651688
- Shamabadi A et al. Emerging drugs for the treatment of irritability associated with autism spectrum disorder. Expert opinion on emerging drugs (2024). PMID 38296815
- De Pol M et al. Endocannabinoid markers in autism spectrum disorder: A scoping review of human studies. Psychiatry research (2021). PMID 34775294
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.